Network Pharmacology Integrated with Molecular Docking Elucidates the Mechanism of Wuwei Yuganzi San for the Treatment of Coronary Heart Disease

Abstract

Introduction: The aim of this study was to investigate the pharmacological mechanism of Wuwei Yuganzi San (WYS) in treating coronary heart disease (CHD) using network pharmacology and molecular docking. Methods: The main active components, related targets, and the target genes related to WYS were investigated by the databases Traditional Chinese Medicine Systems Pharmacology and related articles. Information on the target genes of CHD was acquired through the OMIM database and GeneCards database, and the NCBI Gene Expression Omnibus DataSets (GSE71226) were used to acquire target genes of CHD. A Venn diagram was used to show the common targets of WYS and CHD. The compound-target-disease network was built up by Cytoscape 3.7.2, and the protein–protein interaction (PPI) network was acquired through the STRING database. ClusterProfiler and Pathview packages in RStudio software were used to conduct gene ontology enrichment analysis and KEGG pathway enrichment analysis to reveal the underlying mechanism. Finally, AutoDock Vina software was used to assess the binding affinity of significant ingredients and hub genes. Results: Thirty-four key ingredients of WYS in CHD were screened, which related to 59 targets in CHD. According to the results of enrichment analysis, 59 items in the biological process, 15 items in the molecular function, 10 items in the cellular component, and 52 signaling pathways were associated with efficacy. These processes and pathways were essential for cell survival and were related to several crucial factors of CHD, including a disintegrin and metalloprotease 17 (ADAM17), aldo-keto reductase family 1 member C2 (AKR1C2), albumin (ALB), protein kinase B (AKT1), and alcohol dehydrogenase 1C (ADH1C). Based on the outcomes of the PPI network, we selected ADAM17, AKR1C2, ALB, AKT1, ADH1C, and putative ingredients (sennoside D_qt, quercetin, and procyanidin B-5,3'- O-gallate) to perform molecular docking validation. From the molecular docking outcomes, some vital targets of CHD (including ADAM17, AKR1C2, ALB, AKT1, and ADH1C) could be related to form a stable combination with the putative ingredients of WYS. Conclusions: The network pharmacology and molecular docking study elucidated basically the mechanism of WYS in the treatment of CHD.